Efficient synthesis of nicotinamide mononucleotide

Abstract

The invention provides a process for the preparation of nicotinamide mononucleotide having formula (I):The method involves the protection of nicotinamide riboside by ketalization, followed by phosphorylation and then deprotection to provide nicotinamide mononucleotide.

The invention claimed is: 
     
       1. A process for the preparation of nicotinamide mononucleotide having formula (I): 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein the process comprises the step of reacting a compound of formula (IV): 
       
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently C 1 -C 6  alkyl or, taken together along with the carbon atom to which they are attached, form a 5-7 membered carbocyclic ring, 
         with an acid catalyst in a mixture of solvents to provide nicotinamide mononucleotide, 
         wherein the acid catalyst is trifluoroacetic acid, and 
         wherein the mixture of solvents is a mixture of dichloromethane and water. 
       
     
     
       2. The process of  claim 1 , wherein the reaction is carried out at a temperature of from about 0° C. to about room temperature. 
     
     
       3. A process for the preparation of nicotinamide mononucleotide having formula (I): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein the process comprises the step of reacting a compound of formula (IV): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently C 1 -C 6  alkyl or, taken together along with the carbon atom to which they are attached, form a 5-7 membered carbocyclic ring, 
         with an acid catalyst in a solvent to provide nicotinamide mononucleotide, 
         wherein the solvent is methanol, and 
         wherein the acid catalyst is concentrated hydrochloric acid present in an amount of about 3% (volume/volume) relative to a volume of methanol. 
       
     
     
       4. The process of  claim 3 , wherein the reaction is carried out at a temperature of from about 0° C. to about room temperature. 
     
     
       5. The process of  claim 3 , wherein the reaction is carried out over a time period of about 40 hours or more.